Genome Editing with Engineered Vectors to Correct Neurofibromatosis Type I

Neurofibromatosis type I (NF1) is caused by mutations to the NF1 gene that lead to the development of tumors of the peripheral nervous system. Gene therapy has seen tremendous advances in recent years in the delivery of genes to select tissues to compensate for mutations that cause genetic disease. However, there are two primary challenges that prevent extending these developments to NF1. First, there is currently no method to deliver genes to the cells that initiate tumor development. Second, the NF1 gene is particularly large and is not accommodated within the size-restricted viruses currently used for gene therapy.

We have assembled a team with the particular unique and complementary expertise to overcome both of these challenges and apply the resulting technology to clinically relevant animal models of NF1. First, we will use an innovative strategy to engineer new viruses that target the tumor initiating cells of the peripheral nervous system. Second, we will use CRISPR-based genome editing to restore the mutated NF1 gene, thereby circumventing the need to deliver a copy of the full-length NF1 gene sequence. Finally, we will test the ability of these engineered viruses and genome editing strategies to reduce tumor burden in a mouse model of NF1.

This work will also involve several technological advances that will be generally useful to the field and complement other strategies being explored to apply gene therapy and genome editing to NF1. Our team is further complemented by direct clinical experience with NF1 patients. This project applies some of the most exciting modern biotechnologies to a particularly challenging disease that will be certain to catalyze new innovations for treating NF1.

Investigators

Charles Gersbach, PhD

Duke University

David V. Schaffer, PhD

University of California, Berkeley

David G. Kirsch, MD, PhD

Duke University

Charles Gersbach, PhD

Duke University

David V. Schaffer, PhD

University of California, Berkeley

David G. Kirsch, MD, PhD

Duke University

Current Stage

Discovery

Discovery
In Vivo Proof of Concept
IND Enabling
Clinical Trial Phase 1
Clinical Trial Phase 2
Clinical Trial Phase 3